The multifactorial approach and the food allergen-specific substitutive diet as a tool to manage and ameliorate adverse reactions to foodstuffs in adulthood: study protocol for a randomized controlled trial—the ALASKA study

Background Adverse reactions to foodstuffs (ARFS), specifically food allergy (FA) and food intolerance (FI), are increasing worldwide and represent a major public health concern. Thus, ARFS management, its identification, evaluation, and intervention, must provide a comprehensive solution. Objectives (a) To develop a multifactorial strategy for ARFS management in adults with FA and/or FI; (b) to describe the multiple influential variables in ARFS within the realm of ARFS management; and (c) to design a personalized food allergen-specific substitutive diet (FASSD), as a 6-month dietary treatment option for adults with ARFS and as a component of ARFS management. Methods The ALASKA study will consider the following main variables as part of the ARFS management: (1) demographics and clinical information; (2) symptomatology, food and beverages intake and physical activity; (3) hematobiochemical study; (4) immunology; (5) enzymatic activity; (6) anthropometry, body composition, and physical fitness; (7) QoL; (8) 6-month intervention; (9) end of the study; and (10) other assessments. The FASSD will be designed with special emphasis on the commonly lacking micronutrients in the ARFS population: niacin, Mg, K, P, Ca, Zn, B12, folate, Fe, and fiber. Discussion The ALASKA study protocol has been developed as a global strategy to manage and evaluate ARFS in Spanish adults older than 18 years of age. Approaching ARFS with multiple assessments, as influencing factors, will lead to a novel strategy for ARFS management. The FASSD has been designed as a personalized tool to avoid crucial micronutrient deficiencies that a current strict food allergen avoidance or elimination diet may provoke. Trial registration The protocol has been approved by the Ethics Committee of the UPM (REF.20200602) and registered on ClinicalTrials.gov (NCT05802017). Supplementary Information The online version contains supplementary material available at 10.1186/s13063-024-08307-2.


ANNEX I. GENERAL NUTRITIONAL ADVICE WITH DIETARY RECOMMENDATIONS FOR A HEALTHY LIFESTYLE INSTRUCTIONS:
It is recommended to consume, at least the described number of servings per week and per day (section B "SECOND LEVEL OF THE PYRAMID"), of the food and beverages from each food group.In its place, if you are unable to consume any of the described food or beverages, it is recommended to consume its substitute food or beverage (Annex II).If you have not received Annex II, please follow the recommendations in this Annex only (Annex I).
If you have any questions regarding these recommendations, please contact the research staff at l.pantoja@upm.es,marcela.gonzalez.gross@upm.es, or gi.imfine@upm.es.According to the dietary guidelines for the Spanish population of the Spanish Society of Community Nutrition (SENC) updated in 2019 (1) , the corresponding recommendations are explained below (Figure 1).
Figure 1 Healthy Eating Pyramid.Spanish Society of Community Nutrition (SENC), 2019 (1) A. FIRST LEVEL OR BASE OF THE PYRAMID: • Keep adequate levels of daily physical activity to maintain good health and improve quality of life (60 minutes a day of moderate-intensity physical activity, or the equivalent of 10000 steps a day, with some occasional steps or periods of higher intensity).Note: this present study is not focused in physical activity interventions; therefore, maintain your usual physical activity and sport habits during the time of this present dietary treatment (5 to 6 months).• Dedicate time to food shopping and cooking, as well as to share this knowledge to those closest individuals (promotion of emotional balance).• Adjust the food intake to the physical activity level, in a quantitative and qualitative approach, and viceversa (energetic balance).• Steamed vegetables offer better nutritional and even organoleptic value; and well-cooked eggs are more secured with essential available proteins (healthy cooking techniques).• Water is essential for the maintenance and development of life, so its daily consumption is extremely important.The recommended intake of water is one to two liters of water per day.However, its consumption at libitum or according to your needs of physical and intellectual activity will be the most appropriate.Do not exceed the amount of 6g of total salt (sodium chloride) per day.
• An optional, occasional and moderate consumption of industrial pastries, cakes, sweets, sugary drinks, ice cream and candies is recommended, prioritizing the consumption of pastries made at home using traditional methods and ingredients.
• Moderate or avoid the consumption of alcoholic beverages.The consumption of fermented beverages of low alcohol content and good quality can be assumed in quantities not exceeding two glasses of wine per day in men and one glass per day in women, always referring to adulthood.Consult the research staff in case of chronic diseases or consumption of medicines.
1.If you have resulted equal to or greater than level 3 for any of the following foods, follow the substitution directions detailed below.
• Replace the food and/or beverages to which you have resulted equal to or greater than level 3 and any products that include this foodstuffs as part of their ingredient list (e.g. if you resulted soybean at level equal to or greater than 3; then replace also: soy lecithin, fresh soybeans, soy sauce, tofu, soy vegetable drink, etc.) with any of the substitute foodstuffs described in columns C and D of the Table I. • Maintain your usual diet respecting the number of food and/or beverages that you usually have, your consumption preferences, favorite foods, except for making the change or substitution for the foodstuffs to which you resulted equal to or greater than level 3. • Maintain your usual physical activity and sport habits during the time of this present dietary treatment (5 to 6 months).• When reviewing the list of substitutive foods, make sure you do not have a reaction equal to or greater than level 3 to the foods described in column D.
2. Description of Table I.
• The following table contains the list of substitutive food and/or beverages in alphabetical order.
• The following table contains the list of substitutive food and/or beverages based on the food-allergen panels in type I and type II food allergy for the detection of IgE and IgG4 Ab reactions in human serum samples of AESKUBLOTS (Aesku.Diagnostics GmbH, Wendelsheim, Germany).• The following table contains the list of substitutive food and/or beverages considering mainly their raw form (unless otherwise specified).• The following table contains the list of substitutive food and/or beverages considering the predominant vitamin and mineral of each raw food according to the Spanish Database of Food Composition BEDCA (1) .Particular attention has been paid to the following vitamins and minerals: Niacin, Mg, K, P, Ca, Zn, B12, Folate, Fe and fiber.• The following table contains the list of substitutive food and/or beverages, which substitute the original measured positive foodstuff (foodstuffs with equal to or greater than level 3 result) considering its nutritional content.Substitutive foodstuffs do not always represent a gastronomic substitution.• Foodstuffs of Column A have been omitted in Columns C and D, when possible.

INSTRUCTIONS:
First, we would like to thank you for participating in this study.We will be able to obtain relevant information about the diet you are currently following, and to contribute to the development of the scientific knowledge.
During this interview, it is very important to consider all foodstuffs, food and/or beverages, without forgetting those that you have taken between meals such as: snacks, fruits, pastries, candies, chewing gums or others, as well as those ingredients that are added to meals once prepared: salt, sugar, honey, cocoa, sweetener, etc.Likewise, it is especially important to remember all the consumed beverages such as: water, juice, soft drink, smoothie, tea, coffee, infusion or other additional drink taken either at main meals or between meals.
During this interview, you must also describe all food supplements and/or medication that you have consumed yesterday or during the past 24 hours (e.g., vitamins, minerals, aminoacids or proteins, fat burners, dietary fibers, diuretics, cleansers, probiotics, prebiotics, antioxidants, collagens, appetite control and suppressants, fat and carbohydrate blockers, hyaluronic acid or any other food supplement).

STUCTURE OF THE RECALL INTERVIEW:
1.In the first column, talk about the time of the day at which you started and finished consuming the foodstuffs of each section (i.e., breakfast, between meals, lunch, dinner and meal after dinner), as well as, the place where you consumed them (e.g., at home, friends' house, parents' house, cafeteria, bar, restaurant, workplace, university, during a trip, outdoor picnic, etc.).2. In the second column, provide a general description of the corresponding menu and its food preparation: fried, roasted, grilled, sautéed, stewed, boiled, steamed, etc.In this column, you must also state whether there is a partial or total elimination of any ingredient or foodstuff either because it causes discomfort or due to medical recommendation, such as: salt, milk and dairy products, gluten, eggs, nuts, fish, etc. 3.In the third column, you should detail the type of foodstuffs on each of the mentioned meals, offering special attention to: • Type of dairy product: butter, margarine, cream, yogurt, milk, cheese, shake or other.
• Type of bread: wheat, spelled, buckwheat, rye, whole wheat, corn.And if it is homemade, bar or mold.• Product Brand: (if applicable and remembered).4. Finally, in the last column, describe the consumed amount of each foodstuff, food and/or beverages, as accurately as possible.You can specify the amount consumed using household measurements (glasses, cups, tablespoons, saucepans, capsules, etc.), or also, if you have the information, in grams or milliliters.Remember the leftovers and exclude them from the final count.

GUIDE OF FOOD, BEVERAGES AND FOOD SUPPLEMENTS (EXAMPLES)
Please find below examples of how to describe some food, beverages and food supplements: • The following guide is alphabetically organized.

ALCOHOLIC BEVERAGES
Explain the type of alcoholic beverage: liquor, cognac, whiskey, vodka, gin, rum.Specify the alcohol content, in %, indicated on the label.State the commercial brand, if remembered.

BEER
Explain the type of beer: non-alcoholic, malt beer, wheat beer, rice beer.Specify the consumed amount of beer in: can, bottle, cane, jug, glass, etc.State the commercial brand, if remembered.

BREAD
Explain whether it is white bread, whole wheat, rye, multigrain, rustic, or any other type of bread.Describe if it is homemade, bar or mold.Specify the consumed amount of bread: number of slices or pieces or, at least, the approximate size of the portions, using the visual guide of portion sizes provided by the investigator (interviewer) of this study (1) .State the commercial brand, if remembered.

COFFEE, TEA AND HERBAL INFUSIONS
Describe whether it is regular coffee or decaffeinated coffee.Describe the type of coffee: capsule, soluble and instant.Explain the type of tea or herbal infusion: green tea, black tea, chamomile infusion, pennyroyal, etc. Describe the type and amount of consumed sweetener: white sugar, brown sugar, saccharin, honey, stevia, etc.

EGGS
Explain the animal of origin: chicken, duck, ostrich, quail, etc.If you know it, specify the origin: industrial, ecological, organic.

FISH
Describe the name, type of fish and the serving size using the visual guide of portion sizes provided by the investigator (interviewer) of this study (1) .

FOOD SUPPLEMENTS
Describe the type of food supplement: vitamins, minerals, aminoacids or proteins, fat burners, dietary fibers, diuretics, cleansers, probiotics, prebiotics, antioxidants, collagens, appetite control and suppressants, fat and carbohydrate blockers, hyaluronic acid or any other food supplement.Explain the type of presentation: tablets, capsules, drinks, granules, powder.Describe the consumed amount and the frequency of consumption of food supplements: daily, weekly, monthly.State the commercial brand, if remembered.If possible, provide to the interviewer a photocopy of the composition and list of ingredients of the consumed food supplements.

FRUITS AND VEGETABLES
Explain the type and size of the portion using the visual guide of portion sizes provided by the investigator (interviewer) of this study (1) .

MEAT
Explain the animal of origin (pork, beef, rabbit, chicken), the cut (hip, thigh, breast) and the type of preparation (fried, roasted, grilled, sautéed, stewed, boiled, steamed).In the case of chicken, explain whether you eat the skin or not.

MILK AND DAIRY PRODUCTS
Explain the animal of origin: cow, goat, sheep, etc. Explain the type of milk or dairy product: whole milk, semi-skimmed milk, skimmed milk; Manchego cheese (cured, semi-cured, tender, aged), Roquefort or blue cheese, gouda cheese, parmesan cheese, ricotta cheese or cottage cheese, fresh cheese; liquid yogurt, Greek yogurt (specify flavor; if sweetened, sugared, 0/0 or natural; and if skimmed, whole).Describe whether the foodstuff is: lactose-free, enriched in calcium, omega 3, omega 6, vitamin D, and the consumed amount in glasses, grams, slices or portions.State the commercial brand, if remembered.

NON-ALCOHOLIC BEVERAGES
Explain the type of non-alcoholic beverage: soft drink, fruit juice drink, nectar.Explain the consumed amount in glasses, cups, bottles, etc.

OILS ANS FATS
Describe the type of oils and fats: extra virgin olive oil (EVOO), sunflower oil, butter, margarine.Explain the consumed amount in approximate number of tablespoons.

PASTRIES
Explain the type: croissant, muffins, cakes, palm trees, churros, porras.Describe the consumed amount in serving size using the visual guide of portion sizes provided by the investigator (interviewer) of this study (1) .Describe if it is homemade, bakery or industrial.

PREPARES MEALS
Describe the product, indicating the type of packaging (can, sachet, glass jar, frozen bag, frozen carton) and the consumed amount in portion sizes.State the commercial brand, if remembered.

SALAD
Describe the composition of the salad: lettuce, tomato, onion, spinach, dressing (salt, pepper, vinegar, extra virgin olive oil, sunflower oil) and the consumed amount in portion sizes.

SAUCES
Explain the type of sauce (mayonnaise, ketchup, mustard, pink sauce, soy sauce or hot sauce: chilli, curry) and describe the consumed amount of sauce in tablespoons, ladles, single-dose sachets.State whether they are packaged (industrial), homemade (if homemade, describe their composition).State the commercial brand, if remembered.

SAUSAGE, COLD CUT AND CURED MEAT
Describe the type: turkey ham, pork ham, Iberian ham, pork smoked ham, pork sausage, mortadella.Specify the number of slices or grams.

SOUPS AND MASHED VEGETABLES
Describe the meal composition and explain the quantity in cups, plates, tablespoons, using the visual guide of portion sizes provided by the investigator (interviewer) of this study (1) .

SPICES
Explain the type of spice: salt, basil, thyme, cumin, pepper, parsley, oregano, curry, paprika and the consumed amount in tablespoons or teaspoons, using the visual guide of portion sizes provided by the investigator (interviewer) of this study (1) .

WATER
Specify whether it is bottled, tap, or filtered water.Explain the type of water, mineral, sparkling, still, natural.Explain the consumed amount in number of glasses, glass size or liters, using the visual guide of portion sizes provided by the investigator (interviewer) of this study (1) .

WINE
Explain the type of wine by type of grape, fermentation grade, year and brand.Explain the consumed amount , using the visual guide of portion sizes provided by the investigator (interviewer) of this study (1) .State the commercial brand, if remembered.(If you haven't receive your participant code, please contact the research staff at l.pantoja@upm.es,marcela.gonzalez.gross@upm.es, or gi.imfine@upm.esand request the unique participant code that you will use throughout the entire study as identification.If possible, memorize this code)

SELECT (X) THE DAY OF THE WEEK THAT WAS YESTERDAY:
▢MONDAY ▢TUESDAY ▢WEDNESDAY ▢THURSDAY ▢FRIDAY ▢SATURDAY ▢SUNDAY

FOOD AND/OR BEVERAGES AND FOOD SUPPLEMENTS TIME (HH:MM) AND PLACE OF FOODSTUFFS CONSUMPTION MEAL DESCRIPTION
(First dish, second dish, dessert and drink.Specify the cooking type: fried, roasted, grilled, stewed, boiled, steamed.Specify whether there is a partial or total elimination of any ingredient or foodstuff: gluten, milk, nuts, etc.)

TIME (HH:MM) AND PLACE OF FOODSTUFFS CONSUMPTION MEAL DESCRIPTION
(First dish, second dish, dessert and drink.Specify the cooking type: fried, roasted, grilled, stewed, boiled, steamed.Specify whether there is a partial or total elimination of any ingredient or foodstuff: gluten, milk, nuts, etc.)

TIME (HH:MM) AND PLACE OF FOODSTUFFS CONSUMPTION MEAL DESCRIPTION
(First dish, second dish, dessert and drink.Specify the cooking type: fried, roasted, grilled, stewed, boiled, steamed.Specify whether there is a partial or total elimination of any ingredient or foodstuff: gluten, milk, nuts, etc.)

HOW TO CITE THIS DOCUMENT:
Pantoja-Arévalo L, Gesteiro E, Pérez-Ruiz M, et al.The multifactorial approach and the Food-Allergen Specific Substitutive Diet as a tool to manage and ameliorate adverse reactions to foodstuffs in adulthood: Study Protocol for a Randomized Controlled Trial.The ALASKA study.Supplementary Information.Trials.2024.

Participant code:
(If you haven't receive your participant code, please contact the research staff at l.pantoja@upm.es,marcela.gonzalez.gross@upm.es, or gi.imfine@upm.esand request the unique participant code that you will use throughout the entire study as identification.If possible, memorize this code)

Date since you started following the recommended dietary instructions (provided during your visit):
(DD/MM/YYYY format)

During the last month, have you followed all the dietary recommended indications?
o

Specify below which of the restricted foodstuffs/allergens you have included in your diet during the last month:
Foodstuff/allergen 1: Choose the frequency of consumption of this foodstuff/allergen during the last month:

ANNEX V. BLOOD SAMPLE QUESTIONNAIRE (BSQ)
INSTRUCTIONS: • Complete the following Blood Sample Questionnaire (BSQ) right before the blood sample collection.
• Most of the questions refer to the participant status of the last 24 hours (unless otherwise specified).
• This questionnaire is divided in two sections: clinical and physical activity.
• The grey boxes are reserved to be fulfilled by the researcher (s).Do not complete the grey boxes.

Researcher:
(name or initials of the interviewing investigator.Complete this box only if this questionnaire is carried out with the help of a researcher (interview).Otherwise, leave this box empty.)

Participant code:
(If you haven't receive your participant code, please contact the research staff at l.pantoja@upm.es,marcela.gonzalez.gross@upm.es, or gi.imfine@upm.esand request the unique participant code that you will use throughout the entire study as identification.If possible, memorize this code) Today's date: Today's time: • Choose one morning for the lactose test and another morning, of a different day, for the fructose test.
• The lactose and fructose tests must be carried out in two different days.
• You will need 2 hours to take each test.
• This form has three sections: preparatory period, breath test kit content and test performance.
• If you have any doubt reagarding this instructions, please contact the research staff at l.pantoja@upm.es,marcela.gonzalez.gross@upm.es, or gi.imfine@upm.es

PREPARATORY PERIOD
1. Avoid taking antibiotics for a period of 7 days before performing the test.
2. Avoid taking probiotics (yogurt and fermented milk, kombucha, tempeh, sauerkraut, miso, pickles, kimchi, or similar) for a period of 4 to 5 days before the test.3. Do not smoke at least 1 hour before starting the test or during the test.4. Do not sleep or exercise at least 1 hour before the test or during the test. 5. Do not eat or drink anything other than filtered or bottled water during the test.You can drink as much water as you like before or during the test but do so in small sips of water rather than drinking large amounts at once. 6. Brush your teeth as usual before performing the test.7. Avoid the following foods 24 hours before the test: cereals, bread, pastries, cookies, fruits (including natural juices), sugars and sweeteners (including natural and artificial), milk and dairy products, vegetables, nuts and seeds, chocolate, soy and derivatives and any alcoholic beverage.8.The recommended dietary intake, 24 hours before performing the test, is: fish, chicken or turkey, pork, beef, lamb, sheep, rabbit, eggs; with boiled rice and plain coffee and tea.Note: You can season the food with just 1 pinch of salt and pepper and 1 tablespoon of extra virgin olive oil.9. Fast 8 hours before the start of the test.

BREATH TEST KIT CONTENT
1. 20g of substrate bags (20g of fructose and 20g of lactose powder).2. 10 vacuum-glass tubes (5 glass tubes for lactose and 5 glass tubes for fructose).3. 10 stickers that will be placed after blowing into each of the tubes (stickers with space to fill in the blanks: participant code, substrate, number of the tube, date and time).4. 2 padded transport envelopes (1 for each set of tubes: lactose and fructose).5. 2 disposable devices for air collection.6. 1 bottled water (500ml).7. 1 cleaned and dried glass.8. 1 cleaned and dried spoon.9. 1 chronometer.

TEST PERFORMANCE
1. Make sure you meet the requirements of the "preparatory period" section and check that you have all the materials described in the "breath test kit content" section.2. Fill a cleaned and dried glass with bottled water.3. Pour all the content of 1 bag of substrate (lactose or fructose) into the glass and stir firmly using a cleaned and dried spoon.Note: Do not drink yet.4. Blow into the air inlet hole, inflating the air bag completely of the disposable device for air collection.
While the bag is inflated, insert the cannula from inside the cap into tube #1.Press the tube and blow at the same time for 5 seconds.Inhale air through your nose and exhale through your mouth into the hole of the device.Avoid inhaling the air in the collection bag with your mouth. 5. Fill and place the corresponding sticker on tube #1. 6. Immediately drink all the solution of step 3. 7. Start the timer for 30 minutes.8.After 30 minutes, blow out, following the same instructions as steps 4 and 5 for tube #2.Fill and place the corresponding sticker on tube #2. 9.After 60 minutes blow out, following the same instructions as steps 4 and 5 for tube #3.Fill and place the corresponding sticker on tube #3.10.After 90 minutes, blow out, following the same instructions as steps 4 and 5 for tube #4.Fill and place the corresponding sticker on tube #4.11.After 120 minutes, blow out, following the same instructions as steps 4 and 5 for tube #5.Fill and place the corresponding sticker on tube #5.12.You may take sips of bottled or filtered water whenever you like during the performance of all the test.13.Finally, store the 5 blown tubes in the provided padded envelope.14.Discard the device for air collection and the bag containing the used substrate.15.Repeat the procedure on a different day for the remaining substrate.16.Give the researcher during visit 2 the 2 unsealed padded envelopes, each with 5 blown tubes.

Participant code:
(If you haven't receive your participant code, please contact the research staff at l.pantoja@upm.es,marcela.gonzalez.gross@upm.es, or gi.imfine@upm.esand request the unique participant code that you will use throughout the entire study as identification.If possible, memorize this code)

Today's time:
(HH:MM format) 1. How many adverse events have the participant experienced during this study?: If "1", "2", or "3" selected (options 1, 2 or 3), please specify: Participant code: (If you haven't receive your participant code, please contact the research staff at l.pantoja@upm.es,marcela.gonzalez.gross@upm.es, or gi.imfine@upm.esand request the unique participant code that you will use throughout the entire study as identification.If possible, memorize this code) Today's date: Reminder/rectifications Regarding your data, the instructions provided by you in the initial Informed Consent will be followed.However, you can also rectify any related details, in this space.

Researcher signature, name or initials:
(signature, name or initials of the researcher) THIRD LEVEL • Moderate the consumption of sugar and sugary products.Do not to exceed 10% of the daily energy intake from added sugars.•Moderate the consumption of salt and products with a high concentration of structural or added salt.
POTASSIUM (262mg) ALASKA Study.ALLERGIES AND FOOD INTOLERANCES IN ADULTS AND ATHLETES Pantoja-Arévalo L, Gesteiro E, Pérez-Ruiz M, et al.The multifactorial approach and the Food-Allergen Specific Substitutive Diet as a tool to manage and ameliorate adverse reactions to foodstuffs in adulthood: Study Protocol for a Randomized Controlled Trial.The ALASKA study.Supplementary Information.Trials.2024.Pantoja-Arévalo, L et al.Fragaria vesca VITAMIN C (60mg) POTASSIUM (190mg) PAPAYA, BLACKCURRANT, GUAVA (WITHOUT FRUIT'S PEEL), LICHI, LIME PAPAYA VITAMIN C (64mg) POTASSIUM (214mg) ALASKA Study.ALLERGIES AND FOOD INTOLERANCES IN ADULTS AND ATHLETES Pantoja-Arévalo L, Gesteiro E, Pérez-Ruiz M, et al.The multifactorial approach and the Food-Allergen Specific Substitutive Diet as a tool to manage and ameliorate adverse reactions to foodstuffs in adulthood: Study Protocol for a Randomized Controlled Trial.The ALASKA study.Supplementary Information.Trials.2024.Pantoja-Arévalo, L et al.

ALASKA
Study.ALLERGIES AND FOOD INTOLERANCES IN ADULTS AND ATHLETES Pantoja-Arévalo L, Gesteiro E, Pérez-Ruiz M, et al.The multifactorial approach and the Food-Allergen Specific Substitutive Diet as a tool to manage and ameliorate adverse reactions to foodstuffs in adulthood: Study Protocol for a Randomized Controlled Trial.The ALASKA study.Supplementary Information.Trials.2024.PARTICIPANT CODE: RESEARCHERS: _________________________ (INITIALS OF THE RESEARCHERS) Pantoja-Arévalo L, Gesteiro E, Pérez-Ruiz M, et al.The multifactorial approach and the Food-Allergen Specific Substitutive Diet as a tool to manage and ameliorate adverse reactions to foodstuffs in adulthood: Study Protocol for a Randomized Controlled Trial.The ALASKA study.Supplementary Information.Trials.2024.PARTICIPANT CODE: RESEARCHERS: _________________________ (INITIALS OF THE RESEARCHERS) 24-HOUR DIETARY RECALL INTERVIEW FOOD AND/OR BEVERAGES CONSUMPTION INTERVIEW OF THE PAST 24 HOURS (THE DAY BEFORE) TO THE SUBJECT OF STUDY INTERVIEWER (INITIALS): INTERVIEW DATE: ____ / ____ / 20 PARTICIPANT CODE: ALLERGIES AND FOOD INTOLERANCES IN ADULTS AND ATHLETES Pantoja-Arévalo L, Gesteiro E, Pérez-Ruiz M, et al.The multifactorial approach and the Food-Allergen Specific Substitutive Diet as a tool to manage and ameliorate adverse reactions to foodstuffs in adulthood: Study Protocol for a Randomized Controlled Trial.The ALASKA study.Supplementary Information.Trials.2024.PARTICIPANT CODE: RESEARCHERS: _________________________ (INITIALS OF THE RESEARCHERS) ALLERGIES AND FOOD INTOLERANCES IN ADULTS AND ATHLETES Pantoja-Arévalo L, Gesteiro E, Pérez-Ruiz M, et al.The multifactorial approach and the Food-Allergen Specific Substitutive Diet as a tool to manage and ameliorate adverse reactions to foodstuffs in adulthood: Study Protocol for a Randomized Controlled Trial.The ALASKA study.Supplementary Information.Trials.2024.PARTICIPANT CODE: RESEARCHERS: _________________________ (INITIALS OF THE RESEARCHERS) ALLERGIES AND FOOD INTOLERANCES IN ADULTS AND ATHLETES Pantoja-Arévalo L, Gesteiro E, Pérez-Ruiz M, et al.The multifactorial approach and the Food-Allergen Specific Substitutive Diet as a tool to manage and ameliorate adverse reactions to foodstuffs in adulthood: Study Protocol for a Randomized Controlled Trial.The ALASKA study.Supplementary Information.Trials.2024.Pantoja-Arévalo, L et al.AND FOOD INTOLERANCES IN ADULTS AND ATHLETES Pantoja-Arévalo L, Gesteiro E, Pérez-Ruiz M, et al.The multifactorial approach and the Food-Allergen Specific Substitutive Diet as a tool to manage and ameliorate adverse reactions to foodstuffs in adulthood: Study Protocol for a Randomized Controlled Trial.The ALASKA study.Supplementary Information.Trials.2024.Pantoja-Arévalo, L et al. , Viviana; Lourenço Nogueira, Thais.Guía visual de alimentos y raciones.Editores Médicos S.A. (EDIMSA), editor.2008, 180 p. 2. González-Gross M., Castillo M. J., Moreno L., Nova E., González-Lamuño D., Pérez-Llamas F. et al .Alimentación y valoración del estado nutricional de los adolescentes españoles (Estudio AVENA): Evaluación de riesgos y propuesta de intervención.I. Descripción metodológica del proyecto.Nutr.Hosp.2003; 18(1): 15-28.

oFoodstuff/allergen 2 : 3 . 1 . 1 ALASKA
Never or rarely (none or 1 time during the last month) o Sometimes (2 or 3 times during the last month) o Frequently (4 or 5 times during the last month) o Very frequently (more than 5 times during the last month) o Always (daily or almost daily during the last month.I haven't avoided this foodstuff/allergen at all during the last month) ALASKA Study.ALLERGIES AND FOOD INTOLERANCES IN ADULTS AND ATHLETES Pantoja-Arévalo L, Gesteiro E, Pérez-Ruiz M, et al.The multifactorial approach and the Food-Allergen Specific Substitutive Diet as a tool to manage and ameliorate adverse reactions to foodstuffs in adulthood: Study Protocol for a Randomized Controlled Trial.The ALASKA study.Supplementary Information.Trials.2024.Pantoja-Arévalo, L et al.Choose the frequency of consumption of this foodstuff/allergen during the last month: o Never or rarely (none or 1 time during the last month) o Sometimes (2 or 3 times during the last month) o Frequently (4 or 5 times during the last month) o Very frequently (more than 5 times during the last month) o Always (daily or almost daily during the last month.I haven't avoided this foodstuff/allergen at all during the last month) Foodstuff/allergen 3: Choose the frequency of consumption of this foodstuff/allergen during the last month: o (1) Never or rarely (none or 1 time during the last month) o (2) Sometimes (2 or 3 times during the last month) o (3) Frequently (4 or 5 times during the last month) o (4) Very frequently (more than 5 times during the last month) o (5) Always (daily or almost daily during the last month.I haven't avoided this foodstuff/allergen at all during the last month) (You can expand this list of foodstuffs/allergens as many times as necessary) After the last month, do you think you have improved in some symptomatology aspect?(e.g., I am less constipated, I have noticed less redness on the skin, I am less depressed and anxious).o (1) Yes o (2) No If so (if selected "Yes"), specify in which specific symptomatology have you improved?4.During the last month, how many times have you been in the following situations?4.a.Social events (parties), birthdays, weddings, and any other social event involving food and/or beverages): o (1) Never or rarely (none or 1 time during the last month) o (2) Sometimes (2 or 3 times during the last month) o (3) Frequently (4 or 5 times during the last month) o (4) Very frequently (more than 5 times during the last month) o (5) Always (daily or almost daily during the last month) ALASKA Study.ALLERGIES AND FOOD INTOLERANCES IN ADULTS AND ATHLETES Pantoja-Arévalo L, Gesteiro E, Pérez-Ruiz M, et al.The multifactorial approach and the Food-Allergen Specific Substitutive Diet as a tool to manage and ameliorate adverse reactions to foodstuffs in adulthood: Study Protocol for a Randomized Controlled Trial.The ALASKA study.Supplementary Information.Trials.2024.Pantoja-Arévalo, L et al.PARTICIPANT CODE: RESEARCHERS: _________________________ (INITIALS OF THE RESEARCHERS) 4.b.Out-of-home eating: o (1) Never or rarely (none or 1 time during the last month) o (2) Sometimes (2 or 3 times during the last month) o (3) Frequently (4 or 5 times during the last month) o (4) Very frequently (more than 5 times during the last month) o (5) Always (daily or almost daily during the last month) 4.c.Presence and/or traces of one or more of your restricted foodstuffs/allergens: o (1) Never or rarely (none or 1 time during the last month) o (2) Sometimes (2 or 3 times during the last month) o (3) Frequently (4 or 5 times during the last month) o (4) Very frequently (more than 5 times during the last month) o (5) Always (daily or almost daily during the last month) 4.d.High fat diet o (1) Never or rarely (none or 1 time during the last month) o (2) Sometimes (2 or 3 times during the last month) o (3) Frequently (4 or 5 times during the last month) o (4) Very frequently (more than 5 times during the last month) o (5) Always (daily or almost daily during the last month) 4.e.High amount of food (e.g.free buffets, resort restaurants) o (1) Never or rarely (none or 1 time during the last month) o (2) Sometimes (2 or 3 times during the last month) o (3) Frequently (4 or 5 times during the last month) o (4) Very frequently (more than 5 times during the last month) o (5) Always (daily or almost daily during the last month) 5. Do you think it is worth maintaining this diet?signature or initials: ALASKA Study.ALLERGIES AND FOOD INTOLERANCES IN ADULTS AND ATHLETES Pantoja-Arévalo L, Gesteiro E, Pérez-Ruiz M, et al.The multifactorial approach and the Food-Allergen Specific Substitutive Diet as a tool to manage and ameliorate adverse reactions to foodstuffs in adulthood: Study Protocol for a Randomized Controlled Trial.The ALASKA study.Supplementary Information.Trials.2024.Pantoja-Arévalo, L et al.Gila-Díaz A, Arribas SM, López de Pablo ÁL, López-Giménez MR, Phuthong S, Ramiro-Cortijo D. Development and Validation of a Questionnaire to Assess Adherence to the Healthy Food Pyramid in Spanish Adults.Nutrients.2020; 12(6):1656.2. Ruggeri S, Buonocore P, Amoriello T. New Validated Short Questionnaire for the Evaluation of the Adherence of Mediterranean Diet and Nutritional Sustainability in All Adult Population Groups.Nutrients.2022 Dec 5;14(23):5177.HOW TO CITE THIS DOCUMENT: Pantoja-Arévalo L, Gesteiro E, Pérez-Ruiz M, et al.The multifactorial approach and the Food-Allergen Specific Substitutive Diet as a tool to manage and ameliorate adverse reactions to foodstuffs in adulthood: Study Protocol for a Randomized Controlled Trial.The ALASKA study.Supplementary Information.Trials.2024.Study.ALLERGIES AND FOOD INTOLERANCES IN ADULTS AND ATHLETES Pantoja-Arévalo L, Gesteiro E, Pérez-Ruiz M, et al.The multifactorial approach and the Food-Allergen Specific Substitutive Diet as a tool to manage and ameliorate adverse reactions to foodstuffs in adulthood: Study Protocol for a Randomized Controlled Trial.The ALASKA study.Supplementary Information.Trials.2024.Pantoja-Arévalo, L et al.PARTICIPANT CODE: RESEARCHERS: _________________________ (INITIALS OF THE RESEARCHERS) ALASKA Study.ALLERGIES AND FOOD INTOLERANCES IN ADULTS AND ATHLETES

3 . 1 ALASKA
g., 36.3Do not write units) Has the participant had fever of more than 38ºC during the last 24 hours?o (1) Yes o (2) No 4. Has the participant had any of the following signs and/or symptoms during the last 24 hours?o (1) Cough o (2) Sneezing o (3) Nasal secretion o (4) Itchy skin o (5) Other similar sign and/or symptom o (6) None of the above signs and/or symptoms If "other similar sign and/or symptom" (option 5); which other similar sign or symptom have the participant had during the last 24 hours?(e.g., nasal congestion) ALASKA Study.ALLERGIES AND FOOD INTOLERANCES IN ADULTS AND ATHLETES Pantoja-Arévalo L, Gesteiro E, Pérez-Ruiz M, et al.The multifactorial approach and the Food-Allergen Specific Substitutive Diet as a tool to manage and ameliorate adverse reactions to foodstuffs in adulthood: Study Protocol for a Randomized Controlled Trial.The ALASKA study.Supplementary Information.Trials.2024.Pantoja-Arévalo, L et al.PARTICIPANT CODE: RESEARCHERS: _________________________ (INITIALS OF THE RESEARCHERS) 5. Has the participant had any of the following pathologies and/or diseases during the last 24 hours?o (1) Respiratory infections (flu, rhinitis, common cold, pharyngitis, laryngitis, pneumonia, tracheobronchitis) o (2) Herpes virus o (3) Asthma o (4) Urinary tract infection o (5) Other similar disease and/or pathology o (6) None of the above diseases and/or pathologies If "other similar disease and/or pathology" (option 5); which other similar sign or symptom have the participant had during the last 24 hours?(e.g., influenza) 6.Is the participant in a fasting condition of at least 8 hours?o (1) Yes o (2) NoIf "no" (option 2), specify the current fasting hours of the participant: (i.e., fasting hours of the participant, do not use units or words)If "no" (option 2), write below the date and time of the last food and/or beverage intake of the participant (except for water):(DD/MM/YYYY HH:MM format)7.Has the participant had any complications (infection, hematoma, blood clots) in any bloodextraction/ collection during the last year?o (1) Yes o (2) No If "yes", briefly describe the complication or problem that the participant has had in a blood extraction/ collection during the last year: (e.g.Infection in the extraction area blood) Note: Complete, as a researcher, the "Adverse Event" (Annex VII) in case of major complication during today's blood extraction/collection.8. Has the participant been vaccinated during the last 2 weeks?o (1) Yes o (2) No If "yes", select the vaccine that the participant has received during the last 2 weeks: o (1) Flu o (2) Tetanus o (3) COVID-19 o (4) Allergy o (5) Other vaccine Note: You can select more than 1 option for this question.If "other vaccine" (option 5), state the name of the vaccine that the participant has received during the past 2 weeks: ALASKA Study.ALLERGIES AND FOOD INTOLERANCES IN ADULTS AND ATHLETES Pantoja-Arévalo L, Gesteiro E, Pérez-Ruiz M, et al.The multifactorial approach and the Food-Allergen Specific Substitutive Diet as a tool to manage and ameliorate adverse reactions to foodstuffs in adulthood: Study Protocol for a Randomized Controlled Trial.The ALASKA study.Supplementary Information.Trials.2024.Pantoja-Arévalo, L et al.PARTICIPANT CODE: RESEARCHERS: _________________________ (INITIALS OF THE RESEARCHERS) 9. Did the participant take any medication and/or food supplement during yesterday?o (1) Yes o (2) No If "yes" (option 1), write below the medication and/or food supplement that the participant took yesterday and select below the frequency of consumption (you can also specify the concentration; e.g, paracetamol 1000mg 1/day): A. ______________ o (1) 1/day o (2) 2/day o (3) 3/day o (4) 4/day o (5) > 5/day B. ______________ o (1) 1/day o (2) 2/day o (3) 3/day o (4) 4/day o (o (2) 2/day o (3) 3/day o (4) 4/day o (5) > 5/day If the participant is sex (2) woman; then answer questions from 10 to: 10.Select the current state of the participant: o (1) Menstruation (menstrual cycle) o (2) Pre-menopause (with medical diagnosis) o (3) Menopause (with medical diagnosis) o (4) Post-menopause (with medical diagnosis) If "menstruation or menstrual cycle" (option 1), specify the date of the first day of the participant's menstruation: (DD/MM/YYYY format) If "pre-menopause (with medical diagnosis)" (option 2), specify the date of the first day of the participant's pre-menopause: (DD/MM/YYYY format) ALASKA Study.ALLERGIES AND FOOD INTOLERANCES IN ADULTS AND ATHLETES Pantoja-Arévalo L, Gesteiro E, Pérez-Ruiz M, et al.The multifactorial approach and the Food-Allergen Specific Substitutive Diet as a tool to manage and ameliorate adverse reactions to foodstuffs in adulthood: Study Protocol for a Randomized Controlled Trial.The ALASKA study.Supplementary Information.Trials.2024.Pantoja-Arévalo, L et al.PARTICIPANT CODE: RESEARCHERS: _________________________ (INITIALS OF THE RESEARCHERS)If "menopause (with medical diagnosis)" (option 3), specify the date of the first day of the participant's menopause:(DD/MM/YYYY format)If "post-menopause (with medical diagnosis)" (option 4), specify the date of the first day of the participant's post-menopause: (DD/MM/YYYY format) ALASKA Study.ALLERGIES AND FOOD INTOLERANCES IN ADULTS AND ATHLETES Pantoja-Arévalo L, Gesteiro E, Pérez-Ruiz M, et al.The multifactorial approach and the Food-Allergen Specific Substitutive Diet as a tool to manage and ameliorate adverse reactions to foodstuffs in adulthood: Study Protocol for a Randomized Controlled Trial.The ALASKA study.Supplementary Information.Trials.2024.Pantoja-Arévalo, L et al. the type of transportation that the participant used today to arrive to the blood extraction appointment: o (1) Car or taxi o (2) Bus, subway or train o (3) Motorcycle o (4) Bicycle o (5) Walking o (6) Other type of transportation Note: You can select more than 1 option for this question.If "other type of transportation" (option 6), specify which other (s) type (s) of transportation did the participant used to arrive to the blood extraction appointment: (e.g., electric scooter) 12. Did the participant perform any vigorous physical activity during the last 12 hours such as: lifting heavy objects, swimming, tennis, or any other team sport?o (1) Yes o (2) No If "yes" (option 1), write below the type of vigorous physical activity: (e.g., weightlifting, swimming, tennis) Time of the vigorous physical activity (SINCE): (HH:MM format) Time of the vigorous physical activity (UNTIL): (HH:MM format) Study.ALLERGIES AND FOOD INTOLERANCES IN ADULTS AND ATHLETES Pantoja-Arévalo L, Gesteiro E, Pérez-Ruiz M, et al.The multifactorial approach and the Food-Allergen Specific Substitutive Diet as a tool to manage and ameliorate adverse reactions to foodstuffs in adulthood: Study Protocol for a Randomized Controlled Trial.The ALASKA study.Supplementary Information.Trials.2024.Pantoja-Arévalo, L et al.ALASKA Study.ALLERGIES AND FOOD INTOLERANCES IN ADULTS AND ATHLETES ANNEX VI.BREATH TEST INSTRUCTIONS: LACTOSE AND FRUCTOSE TEST INSTRUCTIONS:

1.a. Date and time of the START of the adverse event 1 :
(DD/MM/YYYY HH:MM format) 1.b.Describe adverse event 1, indicating the consequences that the participant has suffered: 1.c.Date and time of the END of the adverse event 1: (DD/MM/YYYY HH:MM format) 1.d.Date and time of the START of the adverse event 2: (DD/MM/YYYY HH:MM format) 1.e.Describe adverse event 2, indicating the consequences that the participant has suffered: 1.f.Date and time of the END of the adverse event 2: (DD/MM/YYYY HH:MM format)

ALASKA Study. ALLERGIES AND FOOD INTOLERANCES IN ADULTS AND ATHLETES Pantoja
-Arévalo L, Gesteiro E, Pérez-Ruiz M, et al.The multifactorial approach and the Food-Allergen Specific Substitutive Diet as a tool to manage and ameliorate adverse reactions to foodstuffs in adulthood: Study Protocol for a Randomized Controlled Trial.The ALASKA study.Supplementary Information.Trials.2024.

ALASKA Study. ALLERGIES AND FOOD INTOLERANCES IN ADULTS AND ATHLETES Pantoja
-Arévalo L, Gesteiro E, Pérez-Ruiz M, et al.The multifactorial approach and the Food-Allergen Specific Substitutive Diet as a tool to manage and ameliorate adverse reactions to foodstuffs in adulthood: Study Protocol for a Randomized Controlled Trial.The ALASKA study.Supplementary Information.Trials.2024.

PINE NUT + FRIED BROAD BEAN* + PUMPKIN SEED, PINE
* >2 nutrients have been considered due to their importance in the allergenic food.